Adult bone loss is a universal phenomenon, and may lead to bone fracture and osteoporosis. This project investigates the epidemiological, genetic, cross-sectional, longitudinal and cross-cultural aspects of bone loss among participants of the BLSA, and among genetic isolates from Europe, Japan, Australasia, Central America and Africa. As part of our ongoing studies of bone status in the BLSA population, we examined the association between femoral neck bone mineral density (femBMD) measured by dual energy x-ray absorptiometry (DEXA), and cigarette smoking in 391 Caucasian men and 404 Caucasian women aged 21-93 years, who were categorized as current, former, and never smokers (smokers had smoked for 2 or more years). After adjustment for age, weight, height, in men, current and former smokers have significantly lower femBMD than never smokers (0.92plus\minus.02 g/cm2, 0.95plus\minus.01 g/cm2 vs. 0.98plus\minus.01g/cm2, p lesser than 0.05), but this is not found in women (with adjustment for estrogen status). Controlling for years smoked and years since quitting increases the effect in men, but not in women. Reasons for this gender difference will be pursued further, and may be due to differences in exposure. We also examined the effects of weight and obesity on bone mineral density (BMD) in weightbearing and non-weightbearing bones in Caucasian men and women aged 18-96. At the radius, age alone explains 49% of the variance in BMD in women (n=494), and 19% in men (n=974). Weight explains 5-6% of the variance in both sexes, but does not improve the age model. Height alone explains 20% of variance in women and 10% in men; height and age explain 52% of the variance in radial BMD in women, and 22% in men. At the femoral neck, age alone explains 36% of the variance in BMD in women (n=454), and 15% in men (n=393). Weight alone explains 11% of the variance in both sexes; age and weight explain 42% of variance in women and 22% in men. Height alone explains 3% of variance in femoral neck BMD in women, and 6% in men, but does not improve the age or age and weight models. Obesity, measured by percent body fat (estimated from skinfolds) and waist-hip ratio are not independent predictors of BMD at either site. Age and stature predict BMD at the radius, while age and weight explain most of the variance in BMD at the hip.